Diagnostic Photonics, Inc. (DxP) is a medical device company developing an intraoperative imaging system for surgical guidance and real-time assessment of cancer tumor margins based on interferometric synthetic aperture microscopy (ISAM), a novel modality that uses light defraction to assess tissue. Because of the fatty nature of the breast, current intraoperative histopathologic assessments are time consuming and unreliable. This project tests ISAM while the long term goal is to reduce the number of re-excisions for the management of breast cancer by providing rapid, reliable intraoperative margin assessment without tissue destruction. This will result in significant cost savings by reducing repeat operations. It may eventually result in a reduced volume of resection due to the ability to more accurately identify the extent of resection needed. In Phase I, three specific aims will be accomplished. Phase I aims include the development of a handheld probe and instrumentation support, user interface, and sterile disposable needed for execution of in vivo clinical studies as well as a clinical evaluation of ISAM margin detection versus pathology. The clinical goal in Phase I will be an initial evaluation of ISAM by comparing ISAM images against corresponding histology slides. This trial is necessary before proceeding to larger trials and will also serve asa control group for Phase II. The ex vivo assessment of tumor margins using the ISAM device will provide sensitivity and specificity data for the device vs. the gold standard of post-operative histology. The trial results and other data collected such as patient or pathology factors that increase or decrease the rate of margins will allow us to more accurately determine sample size requirements for Phase II. In Phase II, the ISAM technology will be applied in vivo. Correct labeling and assessment of tumor margins has long been considered a weakness of the current margin assessment methods and has been well documented to be unreliable. It is crucial to develop a technique that can assess margins both ex vivo and in vivo in the specimen cavity. Successfully identifying positive margins at the time of the operation allows the surgeon to act on those positive margins immediately, reducing the number of re-excisions. Aims of Phase II include assessment of in vivo margin analysis, evaluation of the utility of the ISAM system and time required during surgery, and the ultimate reduction in repeat surgeries from positive margins.